Gregory B Hammer1, Andrew Lewandowski, David R Drover, David A Rosen, Carol Cohane, Ravinder Anand, Jeff Mitchell, Tammy Reece, Scott R Schulman. 1. 1Department of Anesthesia, Stanford University School of Medicine, Stanford, CA. 2Department of Pediatrics, Stanford University School of Medicine, Stanford, CA. 3The EMMES Corporation, Rockville, MD. 4Department of Anesthesiology, West Virginia University, Morgantown, WV. 5Duke Clinical Research Institute, Durham, NC. 6Department of Anesthesia, University of California-San Francisco School of Medicine, San Francisco, CA.
Abstract
OBJECTIVE:Sodium nitroprusside is a direct-acting vasodilator used to lower blood pressure in the operating room and ICU. The efficacy of sodium nitroprusside has been analyzed in few pediatric randomized trials. This study assesses the efficacy and safety of sodium nitroprusside following at least 12 hours of IV infusion in children. DESIGN: Randomized, double-blind withdrawal to placebo study. SETTING: ICUs. PATIENTS: Pediatric patients younger than 17 years. INTERVENTIONS: Following 12-24 hours of open-label sodium nitroprusside titration, a blinded infusion of sodium nitroprusside or placebo was administered (at the stable rate used at the end of the open-label phase) for up to 30 minutes. MEASUREMENTS AND MAIN RESULTS: The primary efficacy measure was whether control of mean arterial blood pressure was lost, that is, increased above ambient baseline for two consecutive minutes during the blinded phase. The proportion of patients who lost mean arterial blood pressure control in the placebo group (15/19; 79%) was significantly different than those in the sodium nitroprusside group (9/20; 45%) (p = 0.048). Three patients experienced rebound hypertension during the blinded phase, and all were in the placebo group. Serious adverse event rates were low (7/52; 13%), and in only one patient was the serious adverse event determined to be related to sodium nitroprusside by the site investigator. Fourteen patients (27%) had whole blood cyanide levels above 0.5 μg/mL, with high correlation (0.7) between infusion rate and cyanide levels, but there were few clinical signs of cyanide toxicity. CONCLUSIONS:Sodium nitroprusside is efficacious in maintaining mean arterial blood pressure control in children following a 12-hour infusion. Although a high proportion of patients were found to have elevated cyanide levels, toxicity was not observed.
RCT Entities:
OBJECTIVE:Sodium nitroprusside is a direct-acting vasodilator used to lower blood pressure in the operating room and ICU. The efficacy of sodium nitroprusside has been analyzed in few pediatric randomized trials. This study assesses the efficacy and safety of sodium nitroprusside following at least 12 hours of IV infusion in children. DESIGN: Randomized, double-blind withdrawal to placebo study. SETTING: ICUs. PATIENTS: Pediatric patients younger than 17 years. INTERVENTIONS: Following 12-24 hours of open-label sodium nitroprusside titration, a blinded infusion of sodium nitroprusside or placebo was administered (at the stable rate used at the end of the open-label phase) for up to 30 minutes. MEASUREMENTS AND MAIN RESULTS: The primary efficacy measure was whether control of mean arterial blood pressure was lost, that is, increased above ambient baseline for two consecutive minutes during the blinded phase. The proportion of patients who lost mean arterial blood pressure control in the placebo group (15/19; 79%) was significantly different than those in the sodium nitroprusside group (9/20; 45%) (p = 0.048). Three patients experienced rebound hypertension during the blinded phase, and all were in the placebo group. Serious adverse event rates were low (7/52; 13%), and in only one patient was the serious adverse event determined to be related to sodium nitroprusside by the site investigator. Fourteen patients (27%) had whole blood cyanide levels above 0.5 μg/mL, with high correlation (0.7) between infusion rate and cyanide levels, but there were few clinical signs of cyanidetoxicity. CONCLUSIONS:Sodium nitroprusside is efficacious in maintaining mean arterial blood pressure control in children following a 12-hour infusion. Although a high proportion of patients were found to have elevated cyanide levels, toxicity was not observed.
Authors: Rachel D Torok; Jennifer S Li; Prince J Kannankeril; Andrew M Atz; Raafat Bishai; Ellen Bolotin; Stefanie Breitenstein; Cathy Chen; Thomas Diacovo; Timothy Feltes; Patricia Furlong; Michael Hanna; Eric M Graham; Daphne Hsu; D Dunbar Ivy; Dianne Murphy; Lisa A Kammerman; Gregory Kearns; John Lawrence; Brigitte Lebeaut; Danshi Li; Christoph Male; Brian McCrindle; Pierre Mugnier; Jane W Newburger; Gail D Pearson; Vasum Peiris; Lisa Percival; Miriam Pina; Ronald Portman; Robert Shaddy; Norman L Stockbridge; Robert Temple; Kevin D Hill Journal: J Am Heart Assoc Date: 2018-02-10 Impact factor: 5.501